PROJECT SUMMARY
Preimplantation genetic testing for aneuploidy screening (PGT-A) is now widely used to decrease early
pregnancy loss and to increase pregnancy rates, especially in women with advanced reproductive age.
Despite the improved pregnancy outcomes with PGT-A, the current technology has three major limitations that
limit its clinical value. First, standard PGT-A requires invasive embryo biopsy procedures, which can cause
embryo damage or demise. Second, using the few tested non-fetal cells as a surrogate for the entire embryo,
current PGT-A provides only indirect and often inaccurate diagnosis of fetal chromosomal status and can
falsely predict pregnancy success. Third, an extensive process of embryo culture, freezing, and thawing before
embryo transfer is required, which also causes embryo loss and lowers live birth rates. To overcome these
limitations, this proposal will take the first step in developing a novel live embryo imaging method for
aneuploidy detection with the goal of using the tested whole embryo directly for reproduction. This biopsy-free
aneuploidy screening test (“Live PGT-A”) can provide direct and accurate information on all chromosomes in
the entire embryo at the earliest stage without extensive embryo culture, freezing, and thawing. Integrating
complementary expertise in assisted reproduction, bioengineering, fluorescent single-molecule imaging, and
(epi)genomics, this team will develop Live PGT-A in mouse early embryos and examine its safety and
accuracy in detail during this grant period so it can be tested in human embryos in the future as a clinical
diagnostic tool. Specifically, the following aims are proposed: 1) Develop an all-chromosome live imaging
method in somatic cells; 2) Examine the degradation kinetics of fluorescent ribonucleoprotein (fRNP) in mouse
embryos and demonstrate genomic and transcriptomic integrity in the tested embryos; 3) Test whether Live
PGT-A results in healthy offspring. Once this technology is fully developed and the safety is fully tested in
mouse embryos as proposed, it can be readily extended to determine all chromosomes in human embryos, as
well as in sperm and oocytes. The proposed study is highly significant because this novel Live PGT-A method
has high potentials of significantly improving birth outcomes after assisted reproduction by minimizing embryo
loss and wrong diagnosis and thus could one day replace the current PGT-A practice. The technology
developed here also has a wide range of scientific applications. The ability to trace multiple chromosomes at
once in individual live embryos will provide new insights in many essential biological processes during early
embryo development, and enable direct examination of the impact of various aneuploidy on the growth and
development of the embryo.